Analysis of heart rate variability, combined with physiological tests (deep breathing and tilt tests) was used to characterise the effects of atropine and glycopyrrolate on the parasympathetic nervous tone of the heart in healthy male volunteers. The low dose of atropine (120 micrograms) administered as a continuous infusion in 15 min was associated with parasympatomimetic effects estimated by the slowing of the heart rate and an increase of the mean and beat-to-beat heart rate variability. The bradycardia and increase of heart rate variability following infusion of glycopyrrolate (50 micrograms) was less marked and did not differ significantly from that of placebo. The higher doses of atropine (720 micrograms) and glycopyrrolate (300 micrograms) administered as a continuous infusion in 15 min produced an equal vagal cardiac blockade characterised by significant tachycardia and a decrease in overall and beat-to-beat heart rate variability. It is concluded that at low doses the parasympatomimetic action of glycopyrrolate is less marked than that of atropine; and at higher doses only small differences exist between these two muscarinic antagonists in their effects on cardiac vagal outflow, assessed by heart rate and heart rate variability.